Triethylamine → HCID 59312599, compound

HRID 1931555Notes

Reaction equation

HRID 1931555 reaction equation
[NH2:1][C@:2]([CH3:53])([C:49]([CH3:52])([CH3:51])[CH3:50])[CH2:3][O:4][C@@H:5]1[C@@:12]2([CH3:37])[C@@H:13]3[CH2:14][CH2:15][C@H:16]4[C:25]([C@@:8]3([CH2:9][O:10][CH2:11]2)[CH2:7][C@H:6]1[N:38]1[C:42]([C:43]2[CH:48]=[CH:47][N:46]=[CH:45][CH:44]=2)=[N:41][CH:40]=[N:39]1)=[CH:24][CH2:23][C@:22]1([CH3:26])[C@:17]4([CH3:36])[CH2:18][CH2:19][C@@:20]([C@H:31]([CH3:35])[CH:32]([CH3:34])[CH3:33])([CH3:30])[C@H:21]1[C:27]([OH:29])=[O:28].C(N(CC)CC)C.ClC(Cl)(Cl)[C:63]([N:65]=C=O)=[O:64]>ClC(Cl)C>[NH2:65][C:63]([NH:1][C@:2]([CH3:53])([C:49]([CH3:50])([CH3:51])[CH3:52])[CH2:3][O:4][C@@H:5]1[C@@:12]2([CH3:37])[C@@H:13]3[CH2:14][CH2:15][C@H:16]4[C:25]([C@@:8]3([CH2:9][O:10][CH2:11]2)[CH2:7][C@H:6]1[N:38]1[C:42]([C:43]2[CH:44]=[CH:45][N:46]=[CH:47][CH:48]=2)=[N:41][CH:40]=[N:39]1)=[CH:24][CH2:23][C@:22]1([CH3:26])[C@:17]4([CH3:36])[CH2:18][CH2:19][C@@:20]([C@H:31]([CH3:35])[CH:32]([CH3:34])[CH3:33])([CH3:30])[C@H:21]1[C:27]([OH:29])=[O:28])=[O:64]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 76400Trichloroacetyl isocyanateHCID 46871657Ibrexafungerp

Product 1

HCID 59312599HCID 59312599, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-2,3,3-trimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-14-[5-(4-pyridinyl)-1H-1,2,4-triazol-1-yl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid (Example 173, 20 mg, 0.027 mmol) and triethylamine (0.015 mL, 0.11 mmol) in dichloroethane (0.27 mL) was added trichloroacetyl isocyanate (0.004 mL, 0.032 mmoL). The solution was stirred at room temperature for 70 min and then evaporated to dryness. Methanol (0.5 mL) was added to the residue followed by solid potassium carbonate (14.6 mg, 0.11 mmol and the mixture was stirred at room temperature. After 55 min, water (0.1 mL) was added giving a clear solution. The solution was stirred at room temperature for 1 hour and then stored at 5° C. for 64 hours. The solution was evaporated and the residue purified by reverse phase HPLC using a 19×150 mm Sunfire Preparative C18 OBD column (elution with MeCN/water+0.05% TFA). Fractions containing the product were evaporated and freeze-dried from a mixture of ethanol and benzene to give the title compound (not a salt form) as a white solid.

Workup

  1. customevaporated to dryness
  2. additionMethanol (0.5 mL) was added to the residue
  3. stirringthe mixture was stirred at room temperature
  4. waitAfter 55 min
  5. additionwater (0.1 mL) was added
  6. customgiving a clear solution
  7. stirringThe solution was stirred at room temperature for 1 hour
  8. waitstored at 5° C. for 64 hours
  9. customThe solution was evaporated
  10. customthe residue purified by reverse phase HPLC
  11. washC18 OBD column (elution with MeCN/water+0.05% TFA)
  12. additionFractions containing the product
  13. customwere evaporated
  14. dry with materialfreeze-dried from a mixture of ethanol and benzene

Sources & evidence

ORD record
ord-ea5b9049e3674d47a9f2a68824c7796e
Source dataset
uspto-grants-2012_05
Patent number
US08188085B2

Reaction notes

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